Scleroderma or fibrosis of skin caused by a surplus of extracellular matrix protein (collagen) is localized in the skin, or excess collagen may be collected in the kidneys, lungs, gastrointestinal tract, and heart. Scleroderma affects approximately 400,000 persons in the United States every year and according to research studies, annual direct and indirect costs of scleroderma in the United States are $1.5 billion. Morbidity represents the major cost burden, with costs of $819 million (56%) of total costs. The current value of lifetime earnings lost $179 million or $300,000 per death. Direct costs are $462 million (32%) or $4,731 per person annually, indicating that costs are spread over the long disease duration. Currently, there is no known cure and the exact cause remains unknown for scleroderma. Treatment options include, relieving or controlling symptoms. For example, corticosteroids and other immunosuppressive medications are being routinely employed, but have demonstrated only marginal efficacy. Hence there is a critical need for effective but affordable therapies. Recent studies have shown that Interferon-gamma (IFN) is a potential therapy for Scleroderma by inhibiting collagen synthesis. Other studies have shown that transfection of Hepatocyte growth factor (HGF) gene to the bleomycin treated mice prevented the development of Scleroderma and lung fibrosis. While HGF, IFN gamma or other cytokine administration holds therapeutic promise, there are several drawbacks associated with gene therapy, recombinant proteins, or peptide therapy because of instability in solution, and cost-prohibitive production schemes. Angion Biomedica Corp. has identified a small molecule compound, termed Ang1170 that showed antifibrotic effects both in vitro and in vivo. Our preliminary data indicate that Ang1170 has the potential to decrease the expression of fibrotic markers in vitro and decreased pulmonary fibrosis in vivo. The proposed research project is designed to explore the possibility of developing Ang1170 as a new therapeutic approach for the treatment of Scleroderma. Dermal Fibrosis or Scleroderma, is a disease caused by a surplus of extracellular matrix protein localized in the skin, or it may become systemic with excess collagen collecting in the kidneys, lungs, gastrointestinal tract, and heart. Scleroderma affects approximately 400,000 people in the United States every year. There is no known cure for Scleroderma and the exact cause remains unknown. The objective of this application is to evaluate a lead small-molecule drug candidate in clinically relevant models of Scleroderma to develop sufficient data to continue SBIR Phase II studies. [unreadable] [unreadable] [unreadable] [unreadable]